Development and standardisation of ‘time-in-range’ measurement for clinical endpoints in retinal diseases

Abstract

Clear and updated endpoints are required to measure outcomes of a disease course and/or a therapeutic intervention. The aim of this review is to identify a reliable ‘time-in-range’ endpoint of clinical outcomes in ocular conditions, with a particular focus on exudative diseases involving the posterior pole of the eye, and to explore possible applications of this endpoint. A PubMed search was carried out pertaining to: ‘time-in-range’, ‘clinical-outcome’, ‘clinical-endpoint’, ‘clinical trial’, ‘metrics’, ‘retina’, ‘retinopathy’, ‘macular-oedema’, ‘maculopathy’, ‘ophthalmology’, ‘visual-function’, ‘visual acuity end-point’ and ‘OCT’. The results showed that both functional and morphological endpoints have been used in the evaluation of retinal diseases. At present, the most widely accepted and clinically meaningful marker of ocular disease is ‘mean change’ in best corrected visual acuity (BCVA). While comparisons to baseline at various timepoints are commonly recommended to evaluate statistical and clinically relevant differences, few metrics capture the disease course continuously over time. In other medical fields, ‘time-in-range’ has been introduced to provide more complete information on the fluctuations characterising the course of a disease. The application of ‘time-in-range’ on BCVA in exudative diseases involving the posterior pole seems feasible, reliable and applicable in clinical practice. BCVA ‘time-in-range’ offers a useful and practical endpoint in retinal diseases, evaluating both visual function at the end of an observation/treatment and fluctuations in disease over time. It may also be applied to other clinical and morphological endpoints in ocular diseases, including macular thickness. This review presents a hypothesis-generating framework proposing ‘time-in-range’ as a supplementary metric, pending prospective validation.